Effects Of Strychnine On Potassium Ion Channels Of Neurons

This paper aimed to investigate the effects of strychnine on action potential and potassium channel dynamics in neurons, in order to reveal its underlying channel pharmacology mechanisms. The main results are summarized as following.We studyed the effect of strychnine on action potential in cerebral cortical neurons of KM mice and tested whether strychnine had obvious effect on neuron excitability and the underlying ion mechanisms using whole-cell patch current-clamp. The results showed that strychnine could significantly affect the threshold, duration and peak amplitude repetitive firing rate of the action potential and inhibited the voltage-gated potassium channel total currents. These findings suggested that strychnine had neuron excitability by potassium ion channel.Ik plays a major role in the late repolarization of action potential. It can terminate action potential and maintate the resting membrance potential. We studyed the effects of strychnine on delayed rectifier K+channel using whole-cell patch voltage-clamp. Firstly, we investigated effects of strychnine on Ik in neurons cerebral cortical neurons. We found that strychnine could inhibit Ik current in concentration-dependent and voltage-dependent manners and its IC50was1.16μM. Strychnine shifed both the steady-state activation and inactivation curves to more negative voltage. Secondly, we studyed the effects of strychnine on Kv2.1current expressed in HEK293T cells. Our results indicated that:strychnine could accelerate the activation and inactivation of Kv2.1potassium channel. Moreover, strychnine also shifed both the steady-state activation and inactivation curves to more negative voltage.IA plays a major role in the early repolarization of action potential. It can regulate the repetitive firing frequency of neures and affect generation of action potential. We study the effects of strychnine on transient outward potassium channel using whole-cell patch voltage-clamp skill. Firstly, we investigated effect of strychnine on IA in neurons cerebral cortical neurons. We found that strychnine could inhibit Ik current in concentration-dependent and voltage-dependent manners. Strychnine shifed steady-state activation curve to more negative voltage, whereas had no noticeable effect on steady-state inactivation curve. Moreover, strychnine could shifed recovery from fast inactivation of IA to more positive voltage and delayed the transient outward potassium channel recovery from inactivation state. Secondly, we studyed the effect of strychnine on the amplitude of Kv4.3current expressed in HEK293T cells. We found that strychnine could significantly inhibit Kv4.3current and affect steady-state activation curve and recovery from fast inactivation, whereas had no noticeable effect on steady-state inactivation curve.The above results suggest that Ik and IA might be the targets of strychnine, which may explain the mechanisms of excitability effects on cerebral cortical neurons.